Celiac disease (CD) is defined as intolerance to proline- and glutamine-rich gluten proteins of wheat, barley and rye (Koning, Semin Immunopathol), that can cause chronic inflammation in the small intestine (Ludvigsson et al., Gut 2012; 62:43-52). CD patients may present with fatigue, malabsorption, anemia, osteoporosis or neurological signs. The disease is often detected after demonstration of autoantibodies to the enzyme transglutaminase 2 (TG2) (Green et al., N Engl J Med 2007; 357:1731-43). In children the diagnosis can be made without gastroduodenoscopy if the TG2 antibody titer in blood is highly elevated (Husby et al., J Pediatr Gastroenterol Nutr 2012; 54:136-60). In adults however, duodenal biopsy examination and detection of typical histological changes remains a diagnostic premise (AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131:1977-80).
Heterogeneity in the clinical appearance leaves the diagnosis of CD uncertain in many cases. Several patients fail to be referred to gastroduodenoscopy because of false negative antibody tests. Autoantibodies can be present in tissues only but not in blood (Dickey et al., Scand J Gastroenterol 2000; 35:181-3; Kurppa et al., J Pediatr Gastroenterol Nutr 2012; 54:387-91). Frequently, patients present with specific antibody-titers but minor or no changes in the duodenal mucosa (Paparo F et al., Am J Gastroenterol 2005; 100:2294-8). As the small intestine architecture deteriorates gradually by gluten exposure in CD patients (Marsh M N, Gastroenterology 1992; 102:330-54), some are diagnosed later when gastroduodenoscopy is repeated (Kurppa K, et al., Gastroenterology 2009; 136:816-23). Gastroduodenoscopy can only be accomplished by trained physicians. Compared to blood sample-based diagnostic methods, a gastroduodenoscopy is also more invasive and involves longer post intervention surveillance. Some patients also benefit from a gluten-free diet (GFD) although the criteria for diagnosis (AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131:1977-80) are not fulfilled (Kurppa K, et al., Gastroenterology 2009; 136:816-23; Kaukinen et al., Dig Dis Sci 2001; 46-869-87).
Improved compositions and methods for diagnosing CD are needed that clarify diagnosis. Development of a biopsy independent diagnostic test for CD is beneficial both for the patient and for patient care costs.